Direct Imaging of Intracellular Signaling Components That Regulate Bacterial Chemotaxis

PPARγreceptor plays an important role in oxidative stress response. Its agonists can influence vascular contractility in experimental hypertension. Our study was focused on the effects of a PPARγagonist pioglitazone (PIO) on blood pressure regulation, vasoactivity of vessels, and redox-sensitive signaling at the central (brainstem, BS) and peripheral (left ventricle, LV) levels in young prehypertensive rats. 5-week-old SHR were treated either with PIO (10 mg/kg/day, 2 weeks) or with saline using gastric gavage. Administration of PIO significantly slowed down blood pressure increase and improved lipid profile and aortic relaxation after insulin stimulation. A significant increase in PPARγexpression was found only in BS, not in LV. PIO treatment did not influence NOS changes, but had tissue-dependent effect on SOD regulation and increased SOD activity, observed in LV. The treatment with PIO differentially affected also the levels of other intracellular signaling components: Akt kinase increased in the the BS, whileβ-catenin level was down-regulated in the BS and up-regulated in the LV. We found that the lowering of blood pressure in young SHR can be connected with insulin sensitivity of vessels and thatβ-catenin and SOD levels are important agents mediating PIO effects in the BS and LV.

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EMS1 and BRI1 control separate biological processes via extracellular domain diversity and intracellular domain conservation

Nature Communications ◽

10.1038/s41467-019-12112-w ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 11

Author(s):

Bowen Zheng ◽

Qunwei Bai ◽

Lei Wu ◽

Huan Liu ◽

Yuping Liu ◽

...

Keyword(s):

Intracellular Signaling ◽

Physcomitrella Patens ◽

Land Plant ◽

Biological Processes ◽

Expression Domain ◽

Intracellular Domain ◽

Intracellular Signaling Pathway ◽

Domain Conservation ◽

Signaling Components ◽

Early Land

Abstract In flowering plants, EMS1 (Excess Microsporocytes 1) perceives TPD1 (Tapetum Determinant 1) to specify tapeta, the last somatic cell layer nurturing pollen development. However, the signaling components downstream of EMS1 are relatively unknown. Here, we use a molecular complementation approach to investigate the downstream components in EMS1 signaling. We show that the EMS1 intracellular domain is functionally interchangeable with that of the brassinosteroid receptor BRI1 (Brassinosteroid Insensitive 1). Furthermore, expressing EMS1 together with TPD1 in the BRI1 expression domain could partially rescue bri1 phenotypes, and led to the dephosphorylation of BES1, a hallmark of active BRI1 signaling. Conversely, expressing BRI1 in the EMS1 expression domain could partially rescue ems1 phenotypes. We further show that PpEMS1 and PpTPD1 from the early land plant Physcomitrella patens could completely rescue ems1 and tpd1 phenotypes, respectively. We propose that EMS1 and BRI1 have evolved distinct extracellular domains to control different biological processes but can act via a common intracellular signaling pathway.

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Localization of Smads, the TGF-β Family Intracellular Signaling Components During Endochondral Ossification

Journal of Bone and Mineral Research ◽

10.1359/jbmr.1999.14.7.1145 ◽

1999 ◽

Vol 14 (7) ◽

pp. 1145-1152 ◽

Cited By ~ 109

Author(s):

Takashi Sakou ◽

Toshiyuki Onishi ◽

Takuya Yamamoto ◽

Tomonori Nagamine ◽

T. Kuber Sampath ◽

...

Keyword(s):

Intracellular Signaling ◽

Endochondral Ossification ◽

Signaling Components

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Diversification of Disease Resistance Receptors by Integrated Domain Fusions in Wheat and its Progenitors

10.1101/695148 ◽

2019 ◽

Cited By ~ 2

Author(s):

Ethan J. Andersen ◽

Madhav P. Nepal

Keyword(s):

Intracellular Signaling ◽

Defense Responses ◽

Receptor Activation ◽

Alternative Transcripts ◽

Downstream Signaling ◽

Id Genes ◽

Integrated Domains ◽

Effector Recognition ◽

Encoding Genes ◽

Signaling Components

ABSTRACTPathogenic effectors inhibit plant resistance responses by interfering with intracellular signaling mechanisms. Plant Nucleotide-binding, Leucine-rich repeat Receptors (NLRs) have evolved highly variable effector-recognition sites to detect these effectors. While many NLRs utilize variable Leucine-Rich Repeats (LRRs) to bind to effectors, some have gained Integrated Domains (IDs) necessary for receptor activation or downstream signaling. While a few studies have identified IDs within NLRs, the homology and regulation of these genes have yet to be elucidated. We identified a diverse set of wheat NLR-ID fusion proteins as candidates for NLR functional diversification through ID effector recognition or signal transduction. NLR-ID diversity corresponds directly with the various signaling components essential to defense responses, expanding the potential functions for immune receptors and removing the need for intermediate signaling factors that are often targeted by effectors. ID homologs (>80% similarity) in other grasses indicate that these domains originated as functional, non-NLR-encoding genes and were incorporated into NLR-encoding genes through duplication. Multiple NLR-ID genes encode experimentally verified alternative transcripts that include or exclude IDs. This indicates that plants employ alternative splicing to regulate IDs, possibly using them as baits, decoys, and functional signaling components. Future studies should aim to elucidate differential expression of NLR-ID alternative transcripts.

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Transcriptional up-regulation of the TGF-β intracellular signaling transducer Mad of Drosophila larvae in response to parasitic nematode infection

Innate Immunity ◽

10.1177/1753425918790663 ◽

2018 ◽

Vol 24 (6) ◽

pp. 349-356 ◽

Cited By ~ 4

Author(s):

Jelena Patrnogic ◽

Christa Heryanto ◽

Ioannis Eleftherianos

Keyword(s):

Signaling Pathway ◽

Intracellular Signaling ◽

Parasitic Nematode ◽

Transcript Level ◽

Fruit Fly ◽

Parasitic Nematodes ◽

Type I ◽

Drosophila Larvae ◽

Bmp Pathway ◽

Signaling Components

The common fruit fly Drosophila melanogaster is an exceptional model for dissecting innate immunity. However, our knowledge on responses to parasitic nematode infections still lags behind. Recent studies have demonstrated that the well-conserved TGF-β signaling pathway participates in immune processes of the fly, including the anti-nematode response. To elucidate the molecular basis of TGF-β anti-nematode activity, we performed a transcript level analysis of different TGF-β signaling components following infection of D. melanogaster larvae with the nematode parasite Heterorhabditis gerrardi. We found no significant changes in the transcript level of most extracellular ligands in both bone morphogenic protein (BMP) and activin branches of the TGF-β signaling pathway between nematode-infected larvae and uninfected controls. However, extracellular ligand, Scw, and Type I receptor, Sax, in the BMP pathway as well as the Type I receptor, Babo, in the activin pathway were substantially up-regulated following H. gerrardi infection. Our results suggest that receptor up-regulation leads to transcriptional up-regulation of the intracellular component Mad in response to H. gerrardi following changes in gene expression of intracellular receptors of both TGF-β signaling branches. These findings identify the involvement of certain TGF-β signaling pathway components in the immune signal transduction of D. melanogaster larvae against parasitic nematodes .

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Ongoing ingestive behavior is rapidly suppressed by a preabsorptive, intestinal “bitter taste” cue

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00344.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. R1557-R1568 ◽

Cited By ~ 10

Author(s):

Lindsey A. Schier ◽

Terry L. Davidson ◽

Terry L. Powley

Keyword(s):

Taste Aversion ◽

Intracellular Signaling ◽

Bitter Taste ◽

Ingestive Behavior ◽

Nacl Solution ◽

Gi Tract ◽

Molecular Receptors ◽

Signaling Components ◽

Influence Behavior ◽

Infusion Period

The discovery that cells in the gastrointestinal (GI) tract express the same molecular receptors and intracellular signaling components known to be involved in taste has generated great interest in potential functions of such post-oral “taste” receptors in the control of food intake. To determine whether taste cues in the GI tract are detected and can directly influence behavior, the present study used a microbehavioral analysis of intake, in which rats drank from lickometers that were programmed to simultaneously deliver a brief yoked infusion of a taste stimulus to the intestines. Specifically, in daily 30-min sessions, thirsty rats with indwelling intraduodenal catheters were trained to drink hypotonic (0.12 M) sodium chloride (NaCl) and simultaneously self-infuse a 0.12 M NaCl solution. Once trained, in a subsequent series of intestinal taste probe trials, rats reduced licking during a 6-min infusion period, when a bitter stimulus denatonium benzoate (DB; 10 mM) was added to the NaCl vehicle for infusion, apparently conditioning a mild taste aversion. Presentation of the DB in isomolar lithium chloride (LiCl) for intestinal infusions accelerated the development of the response across trials and strengthened the temporal resolution of the early licking suppression in response to the arrival of the DB in the intestine. In an experiment to evaluate whether CCK is involved as a paracrine signal in transducing the intestinal taste of DB, the CCK-1R antagonist devazepide partially blocked the response to intestinal DB. In contrast to their ability to detect and avoid the bitter taste in the intestine, rats did not modify their licking to saccharin intraduodenal probe infusions. The intestinal taste aversion paradigm developed here provides a sensitive and effective protocol for evaluating which tastants—and concentrations of tastants—in the lumen of the gut can control ingestion.

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Computer analysis of the binding reactions leading to a transmembrane receptor-linked multiprotein complex involved in bacterial chemotaxis.

Molecular Biology of the Cell ◽

10.1091/mbc.6.10.1367 ◽

1995 ◽

Vol 6 (10) ◽

pp. 1367-1380 ◽

Cited By ~ 43

Author(s):

D Bray ◽

R B Bourret

Keyword(s):

Computer Analysis ◽

Intracellular Signaling ◽

Bacterial Chemotaxis ◽

Binding Constants ◽

Optimization Methods ◽

Signaling Proteins ◽

Simple Explanation ◽

Multiprotein Complex ◽

Receptor Complexes ◽

Mutant Phenotypes

The chemotactic response of bacteria is mediated by complexes containing two molecules each of a transmembrane receptor and the intracellular signaling proteins CheA and CheW. Mutants in which one or the other of the proteins of this complex are absent, inactive, or expressed at elevated amounts show altered chemotactic behavior and the phenotypes are difficult to interpret for some overexpression mutants. We have examined the possibility that these unexpected phenotypes might arise from the binding steps that lead to active complex formation. A limited genetic algorithm was used to search for sets of binding reactions and associated binding constants expected to give mutant phenotypes in accord with experimental data. Different sets of binding equilibria and different assumptions about the activity of particular receptor complexes were tried. Computer analysis demonstrated that it is possible to obtain sets of binding equilibria consistent with the observed phenotypes and provided a simple explanation for these phenotypes in terms of the distribution of active and inactive complexes formed under various conditions. Optimization methods of this kind offer a unique way to analyze reactions taking place inside living cells based on behavioral data.

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First Insight into the Modulation of Noncanonical NF-κB Signaling Components by Poxviruses in Established Immune-Derived Cell Lines: An In Vitro Model of Ectromelia Virus Infection

Pathogens ◽

10.3390/pathogens9100814 ◽

2020 ◽

Vol 9 (10) ◽

pp. 814

Author(s):

Justyna Struzik ◽

Lidia Szulc-Dąbrowska ◽

Matylda B. Mielcarska ◽

Magdalena Bossowska-Nowicka ◽

Michał Koper ◽

...

Keyword(s):

Cell Lines ◽

Intracellular Signaling ◽

Cell Types ◽

In Vitro Models ◽

Lymphoid Cells ◽

Oncogenic Viruses ◽

Ectromelia Virus ◽

Efficient Replication ◽

Signaling Components

Dendritic cells (DCs) and macrophages are the first line of antiviral immunity. Viral pathogens exploit these cell populations for their efficient replication and dissemination via the modulation of intracellular signaling pathways. Disruption of the noncanonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling has frequently been observed in lymphoid cells upon infection with oncogenic viruses. However, several nononcogenic viruses have been shown to manipulate the noncanonical NF-κB signaling in different cell types. This study demonstrates the modulating effect of ectromelia virus (ECTV) on the components of the noncanonical NF-κB signaling pathway in established murine cell lines: JAWS II DCs and RAW 264.7 macrophages. ECTV affected the activation of TRAF2, cIAP1, RelB, and p100 upon cell treatment with both canonical and noncanonical NF-κB stimuli and thus impeded DNA binding by RelB and p52. ECTV also inhibited the expression of numerous genes related to the noncanonical NF-κB pathway and RelB-dependent gene expression in the cells treated with canonical and noncanonical NF-κB activators. Thus, our data strongly suggest that ECTV influenced the noncanonical NF-κB signaling components in the in vitro models. These findings provide new insights into the noncanonical NF-κB signaling components and their manipulation by poxviruses in vitro.

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